Influence of alpha2-autoreceptor stimulation on the facilitation by angiotensin II and bradykinin of noradrenaline release.

The interaction between alpha(2)-autoreceptors and receptors for angiotensin II and bradykinin was studied in the heart of newborn rats. The tissues were labeled with [3H] noradrenaline and then superfused with cocaine-containing medium and stimulated electrically. Angiotensin II (30-1,000 nM) and bradykinin (10-300 nM) enhanced the evoked overflow of tritium, the maximum increase reaching 52.2 and 72.8%, respectively. In the presence of the selective alpha(2)-adrenoceptor agonist UK-14,304, the maximal effect caused by angiotensin II and bradykinin was enhanced reaching 92.1 and 87.1% for angiotensin II and bradykinin, respectively. On the contrary, in the presence of chelerythrine (a protein kinase C blocker), not only the increment in facilitation by UK-14,304, but to some extent also the basal facilitation caused by angiotensin II and bradykinin were markedly reduced (to 17.3 and 43.2%, respectively). We conclude that: 1. The stimulation of alpha2-autoreceptors enhances the facilitatory responses caused by angiotensin II and bradykinin, confirming that an ongoing alpha2-autoinhibition is required for the facilitatory influence of the peptides. 2. Protein kinase C is involved in the enhancement by angiotensin II and bradykinin of electrically-evoked release of noradrenaline from the nerve terminals.